Transport of oxygen from the lungs to the tissues is fundamental to the functioning of any mammal, and requires the oxygen carrier hemoglobin. Oxygen binds in reversible chemical combination to the prosthetic group, Fe(II) protoporphyrin IX. The mechanism and details of this reaction have been the object of long continued in- vestigations in medicine, physiology, biochemistry, chemistry and biophysics to establish the nature and properties of the reaction at the level of the disciplines mentioned. Recent developments in the kinetics of the hemoglobin-ligand reaction have allowed the binding process to be analyzed in terms of a heme (chemical) component, and a diffusive component describing movement of ligand from the entrance to the heme pocket to the heme. The current objective is to sharpen this analysis, at present in terms of arbitrary kinetic parameters, by linking structure and function, using specifically modified hemoproteins and naturally occurring hemoproteins of known structure to locate the functionally significant residues along the diffusion path. This will advance understanding of the effects of naturally occurring mutations (hemoglobinopathies) of which some 500 are currently known. The main tool will be optical absorbance studies in the nanosecond and picosecond domains.